Aim: To assess the oxidative stress status in rheumatoid arthritis by measuring markers of free radical production, systemic activity of disease, free radical mediated tissue destruction and levels of antioxidant. Methods:Peripheral blood samples were used for all the assays. Total nitric oxide (NO) was quantitatively measured using immunoassay kit. Malondialdehyde (MDA) and vitamin E were measured by spectrophotometric methods.Results: Statistically significant changes were observed in the levels of MDA, vitamin E, total NO and erythrocyte sedimentation rate (ESR) in the patient group. Significant differences were also observed in ESR and vitamin E levels in patients with active disease. Conclusions:Increased oxidative stress status exists, which may lead to connective tissue degradation leading to joint and periarticular deformities in rheumatoid arthritis.
Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that plays a pivotal role in regulating the inflammatory response in rheumatoid arthritis (RA). Although it is controversial whether TNF-α genes are associated with RA susceptibility, they are well known to mediate RA pathogenesis. We review in depth the history, formation and biological action, TNF receptor, role in mediating pathogenesis in RA and mode of action, of anti-TNF-α drugs.
BackgroundHealth concerns unique to women are growing with the large number of women venturing into different trades that expose them to hot working environments and inadequate sanitation facilities, common in many Indian workplaces.ObjectiveThe study was carried out to investigate the health implications of exposures to hot work environments and inadequate sanitation facilities at their workplaces for women workers.DesignA cross-sectional study was conducted with 312 women workers in three occupational sectors in 2014–2015. Quantitative data on heat exposures and physiological heat strain indicators such as core body temperature (CBT), sweat rate (SwR), and urine specific gravity (USG) were collected. A structured questionnaire captured workers perceptions about health impacts of heat stress and inadequate sanitary facilities at the workplace.ResultsWorkplace heat exposures exceeded the threshold limit value for safe manual work for 71% women (Avg. wet bulb globe temperature=30°C±2.3°C) during the study period. Eighty-seven percent of the 200 women who had inadequate/no toilets at their workplaces reported experiencing genitourinary problems periodically. Above normal CBT, SwR, and USG in about 10% women workers indicated heat strain and moderate dehydration that corroborated well with their perceptions. Observed significant associations between high-heat exposures and SwR (t=−2.3879, p=0.0192), inadequate toilet facilities and self-reported adverse heat-related health symptoms (χ2=4.03, p=0.0444), and prevalence of genitourinary issues (χ2=42.92, p=0.0005×10−7) reemphasize that heat is a risk and lack of sanitation facilities is a major health concern for women workers.ConclusionsThe preliminary evidence suggests that health of women workers is at risk due to occupational heat exposures and inadequate sanitation facilities at many Indian workplaces. Intervention through strong labor policies with gender sensitivity is the need of the hour to empower women, avert further health risks, and also enhance productivity for the few million women workers who contribute largely to the country's economy.
In eukaryotes the ubiquitin proteasome pathway plays an important role in cellular homeostasis and also it exerts a critical role in regulating a wide variety of cellular pathways, including cell growth and proliferation, apoptosis, DNA repair, transcription and immune response. Defects in these pathways have been implicated in a number of human pathologies. Inhibition of the ubiquitin proteasome pathway by proteasome inhibitors may be a rational therapeutic approach for various diseases, such as cancer and inflammatory diseases. Many of the critical cytokine and chemokine mediators of the progression of rheumatoid arthritis are regulated by nuclear factor kappa B (NF-κB). In peptidoglycan/polysaccharide-induced polyarthritis, proteasome inhibitors limit the overall inflammation, reduce NF-κB activation, decrease cellular adhesion molecule expression, inhibit nitric oxide synthase, attenuate circulating levels of proinflammatory cytokine interleukin-6 and reduce the arthritis index and swelling in the joints of the animals. Since proteasome inhibitors exhibit anti-inflammatory and anti proliferative effects, diseases characterized by both of these processes such as rheumatoid arthritis might also represent clinical opportunities for such drugs. The regulation of the proteasomal complex by proteasome inhibitors also has implications and potential benefits for the treatment of rheumatoid arthritis. This review summarizes the ubiquitin proteasome pathway, the structure of 26S proteasomes and types of proteasome inhibitors, with their actions, and clinical applications of proteasome inhibitors in various diseases.
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